Solid state characterization of α-tocopherol in inclusion complexes with cyclodextrins

Area of Science:

• Pharmaceutical Science
• Materials Science
• Physical Chemistry

Background:

• Alpha-tocopherol (α-T), a vital nutrient, is an oil-soluble compound sensitive to physical and chemical conditions.
• Complexation with cyclodextrins (CDs) offers a stable, solid alternative to pure α-T.
• Investigating the stability of α-T within cyclodextrin inclusion complexes (InCs) is crucial for pharmaceutical applications.

Purpose of the Study:

• To evaluate the thermal stability of α-T when complexed with cyclodextrins.
• To compare the protective effects of different cyclodextrins against thermal degradation.
• To identify the decomposition products of α-T under accelerated aging conditions.

Main Methods:

• Inclusion complexes (InCs) of α-T with CDs were prepared using lyophilization and kneading methods.
• Formation of InCs was confirmed using IR spectroscopy, differential scanning calorimetry, and 1H-NMR spectroscopy.
• Accelerated aging studies at elevated temperatures (323–343 K) were conducted, with α-T concentration monitored by HPLC and decomposition products analyzed by LC-ESI-MS/MS.

Main Results:

• The thermal decomposition of α-T in InCs and as a pure substance followed first-order kinetics.
• Cyclodextrins significantly protected α-T from thermal decomposition, with natural β-CD showing a stronger protective effect than 2-HP-β-CD.
• The primary decomposition product identified in all samples was the α-T dimer (m/z 859 Da), indicating CDs do not alter the decomposition pathway.

Conclusions:

• Cyclodextrin complexation enhances the thermal stability of α-T, mitigating its degradation.
• The solid-state nature of α-T-CD complexes facilitates the development of new pharmaceutical dosage forms, such as tablets.
• Natural β-CD is a more effective stabilizer for α-T compared to 2-HP-β-CD in these formulations.